Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, multicenter, double-blind, placebo-controlled trial

Tsuyoshi Miyaoka, Motohide Furuya, Jun Horiguchi, Rei Wake, Sadayuki Hashioka, Masaya Thoyama, Kenta Murotani, Norio Mori, Yoshio Minabe, Masaomi Iyo, Shuichi Ueno, Sachiko Ezoe, Syuzo Hoshino, Haruo Seno, Tsuyoshi Miyaoka, Motohide Furuya, Jun Horiguchi, Rei Wake, Sadayuki Hashioka, Masaya Thoyama, Kenta Murotani, Norio Mori, Yoshio Minabe, Masaomi Iyo, Shuichi Ueno, Sachiko Ezoe, Syuzo Hoshino, Haruo Seno

Abstract

Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan) in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted. Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS) and intention-to-treat (ITT). However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54: -0.23 ± 0.08; placebo: -0.03 ± 0.08, P < 0.018), tension (TJ-54: -0.42 ± 0.09; placebo: -0.18 ± 0.09, P < 0.045), and poor impulse control (TJ-54: -0.39 ± 0.10; placebo: -0.07 ± 0.10, P < 0.037). Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores.

Figures

Figure 1
Figure 1
Study design (a) and schedule (b).
Figure 2
Figure 2
Study design and patient flow chart.
Figure 3
Figure 3
(a) Model-estimated marginal means of total and subscale scores of Positive and Negative Syndrome Scale (PANSS) relative to baseline values according to treatment group and follow-up visit (per-protocol set). (A) Total PANSS scores; (B) positive PANSS subscores; (C) negative PANSS subscores; and (D) general psychopathology scores. Error bars indicate standard error of the mean. (b) Model-estimated marginal means of total and subscale scores of Positive and Negative Syndrome Scale (PANSS) relative to baseline values according to treatment group and follow-up visit (intention-to-treat). (A) Total PANSS scores; (B) positive PANSS subscores; (C) negative PANSS subscores; and (D) general psychopathology scores. Error bars indicate standard error of the mean.
Figure 4
Figure 4
Model-estimated marginal means of individual score for Positive and Negative Syndrome Scale (PANSS). Lack of spontaneity and flow, tension, and poor impulsive control items: (a) lack of spontaneity and flow (item N6); (b) tension (item G4); (c) poor impulse control (item G14) scores. Error bars indicate standard error of the mean.

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